Thyroid hormone and estrogen interact to regulate behavior
Thyroid hormone and estrogen interact to regulate behavior
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DOI：
10.1073/pnas.93.22.12581
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发表时间：
1996-10-29
影响因子：
11.1
通讯作者：
Pfaff, DW
中科院分区：
文献类型：
--
作者：
Dellovade, TL;Zhu, YS;Pfaff, DW
环境扰动增加血浆甲状腺激素(T-3)浓度也深刻地影响女性的生殖行为和生理，我们探讨这些影响是否通过T-3受体(TR)和雌激素受体(ER)之间的相互作用来调节。这一假设之所以令人感兴趣，是因为共识T-3反应元件DNA序列的一半位置与ER反应元件(ERE)相同，并且TRs与共识ERE结合。[朱，Y.-S，Yen，P.M.，Chin，W，W，&Pfaff，D，W，(1996)Proc，Natl.阿卡德，科学。美国93,12587-12592]证明了在大鼠下丘脑核提取液中同时存在TRs和ERs，并且两者都能与下丘脑基因前脑啡肽原的启动子结合，并且连接的TRs和ERs之间的相互作用影响前脑啡肽的转录。在本文中，我们证明了TRs和ERs之间的分子相互作用足以调节环境对雌激素控制的生殖行为的影响，高剂量T-3处理的卵巢切除(OVX)大鼠对苯甲酸雌二醇(EB)的反应明显低于单用EB处理的OVX雌性大鼠，相反，与EB处理的OVX雌性大鼠相比，EB处理的甲状腺切除/OVX雌性大鼠表现出显著更高的前凸行为水平显示内源性T-3的作用。甲状腺激素对EB诱导行为的干扰不能用血浆E(2)浓度的降低或EB敏感组织反应性的普遍降低来解释。此外，T-3治疗后，下丘脑EB免疫反应细胞数量显著增加。这些数据表明，T-3可能通过与行为相关的下丘脑神经元核内TR和ER之间的相互作用来减少EB依赖的性行为，首次设想了大脑中两个核激素受体之间相互作用的功能结果。这些结果还为编码环境信号的DNA上的分子相互作用开辟了可能性，为神经元整合的研究开辟了一个新的领域。
Environmental perturbations that increase plasma thyroid hormone (T-3) concentrations also profoundly affect female reproductive behavior and physiology, We explored whether these effects were mediated by interactions between T-3 receptor (TR) and estrogen receptor (ER). This hypothesis was of interest because the half-site of a consensus T-3 response element DNA sequence is identical to an ER response element (ERE), and TRs bind to a consensus ERE. Molecular data presented in the accompanying paper [Zhu, Y.-S., Yen, P. M,, Chin, W, W, & Pfaff, D, W, (1996) Proc, Natl. Acad, Sci. USA 93, 12587-12592] demonstrate that TRs and ERs are both present in rat hypothalamic nuclear extracts and that both can bind to the promoter the hypothalamic gene preproenkephalin and that interations between liganded TRs and ERs affect preproenkephalin transcription, In this paper, we show that molecular interactions between TRs and ERs are sufficient to mediate environmental effects on estrogen-controlled reproductive behavior, Ovariectomized (OVX) rats treated with high doses of T-3 showed significantly lower levels of lordosis behavior in response to estradiol benzoate (EB) compared with OVX females treated with EB alone, Conversely, thyroidectomized/OVX females treated with EB showed significantly greater levels of lordosis behavior compared with OVX females treated with EB, showing the effect of endogenous T-3. Thyroid hormone interference with EB-induced behavior could not be explained by a reduction in plasma E(2) concentrations or by a general reduction in responsiveness of EB-sensitive tissues. Moreover, numbers of hypothalamic EB-immunoreactive cells increased dramatically following T-3 treatment. These data suggest that T-3 may reduce EB-dependent sexual behavior through interactions between TR and ER in the nuclei of behaviorally relevant hypothalamic neurons, envisioning for the first time a functional consequence of interactions between two nuclear hormone receptors in brain. These results also open up the possibility of molecular interactions on DNA encoding environmental signals, a new field for the study of neuronal integration.